The present invention relates to geriatric medicine and, more particularly, to the treatment of senile organic grain syndrome (OBS) by the use of the known drug, 5-o-cyanobenzyl-4,5,6,7-tetrahydrothieno [3,2-c] pyridine methanesulfonate (MS salt).
The phenomenal advances in medicine both therapeutic and preventive, during the past 40 years have significantly increased longevity. This increase in life span, unfortunately, does not necessarily mean that the increasing numbers of elderly people are able to retain a functionally useful and self-supporting capacity during their added years of life. At present there is no drug which is capable of reversing the aging process, it is not likely that such a drug will be discovered in the forseeable future.
Moreover, the central nervous system is particularly susceptible to early or premature senile deterioration. The term aging in itself has little or no pathological significance. Aging is a continuous process which proceeds all the way through life. Senile deterioration is so common and gradual that it could be considered as being a normal condition. It appears that for the great majority of individuals this is a progressive and continuous development which often is not susceptible to identification because it is generally well compensated by human adaptation on the psychological level. However, at a particular point in life (perhaps because of a lack of adaptation), a significant acceleration of aging symptoms may occur, which result in a clinical picture (or spectrum of symptoms) which was not present until that stage. The age at which senile deterioration appears and its degree of intensity varies widely from individual to individual.
OBS has negative sociological, professional and family effects, as is well known. Moreover, senile deterioration as evidenced by Organic Brain Syndrome, often appears too early, too abruptly and/or too intensely. Under these conditions the individual, rather than progressing through harmonious senility, is subjected to pathological senility with all the undesirable psychological and intellectual consequences.
Hollister, in "Drugs for Mental Disorders of Old Age," J.A.M.A. vol. 234, pp. 195-198, 1975 notes that one sixth of the population over 65 years of age have some manifestations of OBS. One-third of the same group have some type of functional disorder such as depression or neurosis; many have both. Hollister also notes that the characteristic clinical hallmark of this condition is an insidious and progressive loss of memory; that the types of organic lesions formed in the aged brain are the well-known senile plaques and neurofibrillary tangles of Alzheimer; that arteriosclerotic changes are found in only about one-third of the patients displaying OBS in old age; that such changes only contribute substantially to the pathologic conditions in about 10% of the cases; and, finally, that a patient may have severe cerebral arteriosclerosis without much clinical evidence of coronary, renal or peripheral arteriosclerosis, and vice versa. A review of the literature suggests that OBS is not significantly related to the existence of arteriosclerosis or other organic problems of old age.
A typical sequence in the development of organic brain syndrome within an individual may be as follows: there is a diminution in mental alertness and memory that may lead to disorientation and confusion with accompanying personality changes such as increasing irritability, hostility, and emotionality (occasionally to the point of paranoia); finally, motivation and initiative may be completely lost, and an essentially vegetative existence for the individual concerned may be evident. Behavioral disturbances such as poor self-care, unsociability, lack of cooperation and just plain "obstreperousness," and such secondary symptoms such as anxiety, depression, fatigue, dizziness, decreased appetite, and sleep loss may be part of this sequence.
The same and similar symptomatic disorders are discussed in "Senile Dementia: Combined Pharmacologic and Psychologic Treatment," by Yesavage, Westphal and Rush in Journal of the American Geriatrics Society, vol. 29, No. 4, (April 1981).
In order to diagnose and assess the degree of OBS and/or senile dementia (SD) existing in a patient or geriatric population, various standard tests or measurement scales have been developed. Among these may be mentioned the Sandoz Clinical Assessment-Geriatric (SCAG), a behavioral rating scale measuring selected symptoms and signs of dementia; the Hamilton Rating Scale for Depression (HRSD); and the Buschke Selective Reminding Scale (BSRT), a psychometric test of memory and hearing.
The Sandoz Clinical Assessment-Geriatric (SCAG) scale has been described in detail by Shader, Harmatz and Salzman, Journal of the American Geriatric Society, 1974, vol. 22, pp. 107-113, and has been found to be a reliable and valid tool for assessing psychopathology in the elderly.
Clinical assessment of cerebral insufficiency in the elderly requiring a reliable and valid measuring instrument, a rating composed of 17 items has been applied, as described in detail by GEORGES, LALLEMAND, COUSTENOBLE and LORIA, Therapie (FRANCE), 1977, vol. 32, 2, pp. 173-180, for this purpose. Factor analysis results have shown that the factors identified appeared to well represent the content areas tapped by the rating scale which possesses a construct validity in geriatrics.
Numerous drugs have been suggested for use in the treatment of OBS and SD, many of which are discussed in "A Review of Some Current Drugs Used in the Pharmacotherapy of Organic Brain Syndrome," by Scott in Physiology and Cell Biology of Aging (Aging, vol. 8), edited by Cherkin et al., Raven Press, New York (1979). The ergot aklaloids are the drugs most commonly used world-wide for cognitive disorders; as far as is known, the only such drug clinically available in the United States is dehydroxyergotoxine mesylate (DEM) sold under the trademark "Hydergine."
Yesavage et al. supra. have noted, however, that treatment with ergot alkaloids is quite complicated because of their diverse and undesirable pharmacologic effects.
It is apparent therefore that a need remains in the art for a drug for the treatment of OBS or SD which is safe and reliable and which does not exhibit the complex and disadvantageous pharmacologic effects of DEM.